Howard E. Gendelman, MD

Howard E. Gendelman

Professional Summary
Research
Representative Publications
Biographical Information
Visit Dr. Gendelman's Lab

HOWARD E. GENDELMAN MD
Margaret R. Larson Professor of Internal Medicine and Infectious Diseases
Chair, Department of Pharmacology and Experimental Neuroscience

Durham Research Center, 8008
985880 Nebraska Medical Center
Omaha, NE 68198-5880

Phone: 402-559-8920
E-mail: hegendel@unmc.edu


In the news:

KETV.com, January 10, 2014
UNMC researches test vaccine for Parkinson's disease

UNMC Today, July 10, 2013
Investigators to Launch Clinical Trial Testing Parkinson's Therapy

Omaha World-Herald, Live Well, July 1, 2013
One-two punch vs. Parkinson's: meds and a machine

News Archive


Professional Summary

Dr. Howard E. Gendelman is the Margaret R. Larson Professor of Internal Medicine and Infectious Diseases, Chairman of the Department of Pharmacology and Experimental Neuroscience, and Director of the Center for Neurodegenerative Disorders at the University of Nebraska Medical Center. Dr. Gendelman is credited in unraveling how functional alterations in brain immunity induce metabolic changes and ultimately lead to neural cell damage for a broad range of infectious, metabolic and neurodegenerative disorders. These discoveries have had broad implications in developmental therapeutics aimed at preventing, slowing or reversing neural maladies. He is also credited for the demonstration that AIDS dementia is a reversible metabolic encephalopathy; a finding realized at the University of Nebraska Medical Center. His work has led to novel immunotherapy and nanomedicine strategies for Parkinson’s and viral diseases currently being tested in early clinical trials as a result of intense translational investigations.

Dr. Gendelman obtained a Bachelor’s degree in Natural Sciences and Russian Studies with honors from Muhlenberg College and his M.D. from the Pennsylvania State University-Hershey Medical Center where he was the 1999 Distinguished Alumnus. He completed a residency in Internal medicine at Montefiore Hospital, Albert Einstein College of Medicine and was a Clinical and Research Fellow in Neurology and Infectious Diseases at the Johns Hopkins University Medical Center. He occupied senior faculty and research positions at the Johns Hopkins Medical Institutions, the National Institute of Allergy and Infectious Diseases, the Uniformed Services University of the Health Sciences Center, the Walter Reed Army Institute of Research, and the Henry Jackson Foundation for the Advancement in Military Medicine before joining the University of Nebraska Medical Center faculty in March of 1993. He retired from the US Army with the rank of Lieutenant Colonel. Dr. Gendelman has authored over 400 peer-reviewed publications, edited nine books and monographs, holds eight patents, is the Editor-In-Chief and Founder of the Journal of Neuroimmune Pharmacology along with service on numerous editorial boards, national and international scientific review and federal and state committees. He has been an invited lecturer to more than 200 scientific seminars and symposia and the recipient of numerous local, national and international honors. These, include, but are not limited to, the Henry L. Moses Award in Basic Science; the Carter-Wallace Fellow for Distinction in AIDS Research, the David T. Purtilo Distinguished Chair of Pathology and Microbiology, the UNMC Scientist Laureate; NU Outstanding Research and Creativity and the Joseph Wybran Distinguished Scientist Awards. Dr. Gendelman was named a J. William Fulbright Research Scholar at the Weizmann Institute of Science in Israel. In 2001, he received the prestigious Jacob Javits Neuroscience Research Award and the Career Research Award in Medicine from UNMC.

He is included amongst a selective scientific group listed on highly cited.com as one of the top cited scientists in his field. Dr. Gendelman has trained more than forty scientists (students and postdoctoral fellows) who have themselves developed independent successful careers. Under his leadership, the department now holds scores of independent R01s or equivalent grants, four program project grants, and shares two program developmental awards. His leadership is credited with the growth of the Department of Pharmacology and Experimental Neuroscience at the University of Nebraska Medical Center to be amongst the top-like ranked and federally funded departments (top ten) nationwide; a particularly noted feat as its position was 77 when he assumed its leadership.

Research:

The neuroregeneration laboratory provides the student or postdoctoral fellow with broad research experiences in diagnostics, pathogenic mechanisms and therapies for neurodegenerative disorders.

The major focus for our research is on the role played by glial inflammatory activities in brain disease. The work bridges immunology, neuroscience and pharmacology and crosses disease barriers for studies of HIV-1-associated neurocognitive disorders, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). The major goal is to use immune-based approaches to reverse nerve cell damage.

The laboratory initiative is divided into specific programs with cross-disciplinary support provided through experienced senior scientists. Specific expertise is available in proteomics, immunology, molecular neuroscience, infectious disease, neurophysiology and neuropathogenesis.

Research priorities in nanomedicine focuses on drug delivery to the central nervous system using "smart" drugs that are packaged into immunocytes and use “Trojan horse” cell-based mechanisms to by-pass the blood-brain barrier and enter diseased brain areas. These are intertwined with studies of disease pathogenesis focused on studies of the biophysical and effector cell properties of blood-borne macrophages that modulate leukocyte entry and glial immunity.

Our nanomedicine program provides laboratory experiences in nanoformulations and physical chemistry linked to characterization of nanoparticles as well as animal studies of disease pathobiology using "state of the art" drug delivery systems. Coordinate drug testing (anti-inflammatory, neuroprotective and anti-retroviral) in HIV-1 encephalitis (HIVE) and PD are pursued with adjunctive drugs distinct or part of the nanomedicine efforts.

This program is part of multiple National Institutes of Health grant efforts that involve scientists at the University of Nebraska Medical Center (College of Medicine and College of Pharmacy), the University of Rochester, and Columbia University College of Physicians and Surgeons. The focus is to perform translational research that would move quickly from animals to humans and currently involves human phase I testings.

Our neuroimmunologic and vaccine approaches have shown tremendous success in recent years for their abilities to induce protective immunity and protect against ongoing neurodegeneration. These are being pursued in animal models of HIVE, PD and ALS.

Our proteomic and metabolomic studies involve basic cell biology and molecular studies of virus-cell interactions in the setting of abused drugs.

All together this is a rich offering in scientific disciplines and relevant human disease models that can readily translate from the laboratory bench to the clinic.

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Representative Publications:

  1. Roy, U., McMillan, J., Alnouti, Y., Gautum, N., Smith, N., Balkundi, S., Dash, P., Gorantla, S., Martinez-Skinner, A., Meza, J., Kanmogne, G., Swindells, S., Cohen, S.M., Mosley, R.L., Poluektova, L., Gendelman, H.E. Pharmacodynamic and Antiretroviral Activities of Combination Nanoformulated Antiretrovirals in HIV-1-Infected Human PBL-Reconstituted Mice. In press, J Infect Dis, 2012. PMC Journal – in process
  2. Dash, P., Gendelman, H.E., Roy, U., Balkundi, S., Alnouti, Y., Mosley, R.L., Gelbard, H.A., McMillan, J., Gorantla, S., Poluektova, L. Long-Acting NanoART Elicits Potent Antiretroviral and Neuroprotective Responses in HIV-1 Infected Humanized Mice. In press, AIDS, 2012. PMC Journal – in process
  3. Kanmogne, G.D., Singh, S., Roy, U., Liu, X., McMillan, J., Gorantla, S., Balkundi, S., Smith, N., Alnouti, Y., Gautam, N., Zhou, Y., Poluektova, L., Kabanov, A., Bronich, T., Gendelman, H.E.  Mononuclear Phagocyte Intercellular Crosstalk Facilitates Transmission of Cell Targeted Nanoformulated Antiretroviral Drugs to Human Brain Endothelial Cells., Intl J Nanomedicine, 2012:7;2373-2388.
  4. Zhao Y, Haney MJ, Klyachko NL, Li S, Booth SL, Higginbotham SM, Jones J, Zimmerman MC, Mosley RL, Kabanov AV, Gendelman HE, Batrakova EV. Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles. Nanomedicine (Lond). 2011 Jan;6(1):25-42
  5. Boska M, Liu Y, Uberti M, Sajja BR, Balkundi S, McMillan J, Gendelman HE. Registered bioimaging of nanomaterials for diagnostic and therapeutic monitoring. J Vis Exp. 2010 Dec 9;(46)
  6. Balkundi S, Nowacek AS, Roy U, Martinez-Skinner A, McMillan J, Gendelman HE. Methods development for blood borne macrophage carriage of nanoformulated antiretroviral drugs. J Vis Exp. 2010 Dec 9;(46)
  7. Bressani RF, Nowacek AS, Singh S, Balkundi S, Rabinow B, McMillan J, Gendelman HE, Kanmogne GD. Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug uptake and carriage. Nanotoxicology. 2010 Dec 22. [Epub ahead of print]
  8. Kraft-Terry S, Gerena Y, Wojna V, Plaud-Valentin M, Rodriguez Y, Ciborowski P, Mayo R, Skolasky R, Gendelman HE, Meléndez LM. Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants. Proteomics Clin Appl. 2010 Sep;4(8-9):706-14
  9. Nowacek AS, Balkundi S, McMillan J, Roy U, Martinez-Skinner A, Mosley RL, Kanmogne G, Kabanov AV, Bronich T, Gendelman HE. Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages. J Control Release. 2010 Nov 23. [Epub ahead of print]
  10. Gorantla S, Makarov E, Finke-Dwyer J, Castanedo A, Holguin A, Gebhart CL, Gendelman HE, Poluektova L Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. Am J Pathol. 2010 Dec;177(6):2938-49
  11. Huang X, Stone DK, Yu F, Zeng Y, Gendelman HE. Functional proteomic analysis for regulatory T cell surveillance of the HIV-1-infected macrophage. J Proteome Res. 2010 Dec 3;9(12):6759-73
  12. Gelbard HA, Dewhurst S, Maggirwar SB, Kiebala M, Polesskaya O, Gendelman HE. Rebuilding synaptic architecture in HIV-1 associated neurocognitive disease: a therapeutic strategy based on modulation of mixed lineage kinase. Neurotherapeutics. 2010 Oct;7(4):392-8
  13. Gong N, Liu J, Reynolds AD, Gorantla S, Mosley RL, Gendelman HE. Brain ingress of regulatory T cells in a murine model of HIV-1 encephalitis.J Neuroimmunol. 2010 Sep 14.[Epub ahead of print]
  14. Wiederin JL, Donahoe RM, Anderson JR, Yu F, Fox HS, Gendelman HE, Ciborowski PS. Plasma proteomic analysis of simian immunodeficiency virus infection of rhesus macaques. J Proteome Res. 2010 Sep 3;9(9):4721-31
  15. Gorantla S, Makarov E, Roy D, Finke-Dwyer J, Murrin LC, Gendelman HE, Poluektova L. Immunoregulation of a CB2 receptor agonist in a murine model of neuroAIDS. J Neuroimmune Pharmacol. 2010 Sep;5(3):456-68
  16. Kosloski LM, Ha DM, Hutter JA, Stone DK, Pichler MR, Reynolds AD, Gendelman HE, Mosley RL. Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases. J Neurochem. 2010 Sep 1;114(5):1261-76
  17. Gorantla S, Makarov E, Finke-Dwyer J, Gebhart CL, Domm W, Dewhurst S, Gendelman HE, Poluektova LY. CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice. J Immunol. 2010 Jun 15;184(12):7082-91
  18. Brynskikh AM, Zhao Y, Mosley RL, Li S, Boska MD, Klyachko NL, Kabanov AV, Gendelman HE, Batrakova EV. Macrophage delivery of therapeutic nanozymes in a murine model of Parkinson's disease. Nanomedicine (Lond). 2010 Apr;5(3):379-96
  19. Kiyota T, Okuyama S, Swan RJ, Jacobsen MT, Gendelman HE, Ikezu T. CNS expression of anti-inflammatory cytokine interleukin-4 attenuates Alzheimer's disease-like pathogenesis in APP+PS1 bigenic mice. FASEB J. 2010 Aug;24(8):3093-102. Epub 2010 Apr 6
  20. Yao H, Yang Y, Kim KJ, Bethel-Brown C, Gong N, Funa K, Gendelman HE, Su TP, Wang JQ, Buch S. Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration. Blood. 2010 Jun 10;115(23):4951-62
  21. Nowacek AS, McMillan J, Miller R, Anderson A, Rabinow B, Gendelman HE. Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics. J Neuroimmune Pharmacol. 2010 Dec;5(4):592-601
  22. Reynolds AD, Stone DK, Hutter JA, Benner EJ, Mosley RL, Gendelman HE. Regulatory T cells attenuate Th17 cell-mediated nigrostriatal dopaminergic neurodegeneration in a model of Parkinson's disease. J Immunol. 2010 Mar 1;184(5):2261-71
  23. Batrakova EV, Li S, Brynskikh AM, Sharma AK, Li Y, Boska M, Gong N, Mosley RL, Alakhov VY, Gendelman HE, Kabanov AV. Effects of pluronic and doxorubicin on drug uptake, cellular metabolism, apoptosis and tumor inhibition in animal models of MDR cancers. J Control Release. 2010 May 10;143(3):290-301
  24. Gendelman H.E., Ding S., Gong N., Liu J., Ramirez S.H., Persidsky Y., Lee Mosley R., Wang T, Volsky D.J., and Xiong H. Monocyte Chemotactic Protein-1 Regulates Voltage-Gated K(+) Channels and Macrophage Transmigration. J Neuroimmune Pharmacol. 4(1):47-592009 PMCID: PMC2657224
  25. Dou, H., Grotepas, C.B., Zeng, C., Destache, C.J., Shlyakhtenko, L., Chaubal, M., Werling, J., Kipp, J., Rabinow, B.E., and Gendelman, H.E. Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of NeuroAIDS. J. Immunol. Jul 1;183(1):661-92009
  26. Beduneau, A., Grotepas, C.B., Kabanov, A., Rabinow, B.E., Gong, N., Mosely, R.L., Boska, M.D., Dou, H., and Gendelman, H.E. Facilitated monocyte-macrophage uptake and tissue distribution of immunoglobulin coated superparamagnetic iron-oxide nanoparticles. PLoS ONE, 4(2):e4343 2009 PMCID: PMC2629545
  27. Kadiu, I., Wang, T., Schlautman, J.D., Dubrovsky, L, Ciborowski, P., Bukrinsky, M., and Gendelman, H.E. HIV-1 transforms the monocyte plasma membrane proteome. Cell Immunol., 258(1):44-58 2009 PMCID: PMC2746502
  28. Reynolds, A.D., Stone, D.K., Mosley, R.L, and Gendelman, H.E. Nitrated alpha synuclein induced alterations in microglial immunity is regulated by CD4+ T cell subsets, J. Immunol., 182(7):4137-49 2009PMCID: PMC2659470
  29. Liu, J., Gong, N., Huang, X., Reynolds, A.D., Mosley, R.L., and Gendelman, H.E. Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1 associated neurodegeneration. J. Immunol. 15;182(6):3855-652009 PMCID: PMC2661207
  30. Schifitto, G, Zhong, J., Gill, D., Peterson, D.R., Gaugh, M.D., Zhu, T., Tivarus, M., Cruttenden, K, Maggirwar, S.B., Gendelman, H.E., Dewhurst, S., and Gelbard, H.A. Lithium therapy for HIV-1 associated neurocognitive impairment. J. Neurovirol. 52(2);176-1862009
  31. Kiyota T., Yamamoto, M., Schroder, B., Jacobsen, M.T., Swan, R.J., Lambert, M.P., Klein, W.L., Gendelman, H.E., Ransohoff, R.M. and Ikezu, T. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Molecular Ther 17 (5):803-9 2009PMCID: PMC2709991
  32. Nowacek. A. and Gendelman, H.E. NanoART, neuroAIDS and CNS drug delivery. Nanomedicine, Jul;4(5):557-74 2009PMID: PMC2746674
  33. Reynolds, A.D., Stone, D.K., Mosley, R.L., and Gendelman, H.E. Proteomic studies of nitrated alpha-synuclein microglia regulation by CD4+CD25+ T cells. J. Proteome Res. 8(7):3497-5112009 PMCID: PMC2747638
  34. Huang, X. Reynold, A.D., Mosley, R.L. and Gendelman, H.E. CD4+ T cells in the pathobiology of neurodegenerative disorders. J. Neuroimmunol., 25;211(1-2):3-152009 PMCID: PMC2696588
  35. Eggert, D., Dash, P.K., Serradji, N., Dong, C-Z., Clayette, P., Heymans, F., Dou, H., Gorantla, S., Gelbard, H.A., Poluektova, L., and Gendelman, H.E. Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders. J. Neuroimmunol. 213:47-592009 PMCID: PMC2757154
  36. Nowacek, A., Kosloski, L.M. and Gendelman, H.E. Neurodegenerative disorders and nanoformulated drug development. Nanomedicine Jul;4(5):541-55 2009 PMCID: PMC2727651
  37. Gendelman, H.E. Preface. Lentiviruses and macrophages: Molecular and Cellular Interactions Eds. Moira Desport, 2009
  38. Keblesh, J.P., Dou, H., Gendelman, H.E. and Xiong, H. 4-Aminopyridine improves spatial memory in a murine model of HIV-1 encephalitis. J. Neuroimmune Pharmacol. Sep;4(3):317-272009
  39. Joseph, J., Clifford, D., Douglas, S.D., Fox, H., Gendelman, H.E., Gonzalez-Scarano, F., Grant, I., Major, E., McArthur J. and the NeuroAIDS research participants. J. Neuroimmune Pharmacol. 4(3):283-972009 PMCID: PMC2719735
  40. Kiyota, T., Yamamoto, M., Xiong, H., Lambert, M.P., Klein, W.L., Gendelman, H.E., Ransohoff, R.M. and Ikezu, T. CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction. PLoS One. Jul10;4(7);e6197 2009 PMCID: PMC2703798
  41. Stone, D.K., Reynolds, A.D., Mosley, R.L., and Gendelman, H.E. Innate and adaptive immunity for the pathobiology of Parkinson's disease. Antiox. Redox. Signaling Sep;11(9):2151-66 2009PMCID: PMC2788126
  42. Liu, Y., Uberti, M., Mosley, R.L., Gendelman, H.E. and Boska, M. An Image Warping Technique for Rodent Brain MRI-Histology Registration Based On Thin-Plate Splines with Landmark Optimization. In press, Proc. SPIE Med. Imaging 2009
  43. Uberti, M., Liu, Y., Dou, H., Mosley, R.L., Gendelman, H.E. and Boska, M. Registration of in vivo MR to histology of rodent brains using blockface imaging. In press, Proc. SPIE Med. Imaging 2009

Additional publications in pubmed.gov

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Dr. Gendelman's biographical information

Visit Dr. Gendelman's laboratory

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